Cai_2018_Eur.J.Med.Chem_157_161

Reference

Title : Donepezil-butylated hydroxytoluene (BHT) hybrids as Anti-Alzheimer's disease agents with cholinergic, antioxidant, and neuroprotective properties - Cai_2018_Eur.J.Med.Chem_157_161
Author(s) : Cai P , Fang SQ , Yang HL , Yang XL , Liu QH , Kong LY , Wang XB
Ref : Eur Journal of Medicinal Chemistry , 157 :161 , 2018
Abstract :

The multifactorial nature of Alzheimer's disease (AD) calls for the development of multitarget agents addressing key pathogenic processes. A novel family of donepezil-butylated hydroxytoluene (BHT) hybrids were designed, synthesized and evaluated as multifunctional ligands against AD. The optimal compound 7d displayed a balanced multifunctional profile covering an intriguing acetylcholinesterase (AChE) inhibition (IC50, 0.075muM for eeAChE and 0.75muM for hAChE) and Monoamine oxidase B (MAO-B) inhibition (IC50, 7.4muM for hMAO-B), excellent antioxidant activity (71.7muM of IC50 by DPPH method, 0.82 and 1.62 trolox equivalent by ABTS method and ORAC method respectively), and inhibitory effects on self-induced, hAChE-induced Abeta aggregation. Moreover, 7d possessed neuroprotective potency against H2O2-induced oxidative damage on PC12cells and Lipopolysaccharides (LPS)-stimulated inflammation on BV2 cells. Compound 7d was capable of penetrating BBB and presented good liver microsomal metabolic stability. Importantly, compound 7d could dose-dependently reverse scopolamine-induced memory deficit in mice without acute toxicity. Taken together, those outstanding results highlight the donepezil-BHT hybrid 7d as a promising prototype in the research of innovative compound for AD.

PubMedSearch : Cai_2018_Eur.J.Med.Chem_157_161
PubMedID: 30096650

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Citations formats

Cai P, Fang SQ, Yang HL, Yang XL, Liu QH, Kong LY, Wang XB (2018)
Donepezil-butylated hydroxytoluene (BHT) hybrids as Anti-Alzheimer's disease agents with cholinergic, antioxidant, and neuroprotective properties
Eur Journal of Medicinal Chemistry 157 :161

Cai P, Fang SQ, Yang HL, Yang XL, Liu QH, Kong LY, Wang XB (2018)
Eur Journal of Medicinal Chemistry 157 :161